Rimegepant for Irritable Bowel Syndrome

Overseen By Deborah Eckert, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Depression, Substance abuse, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rimegepant can reduce stomach pain in individuals with certain types of irritable bowel syndrome (IBS) that do not involve constipation. Participants will receive either rimegepant or a placebo (a pill with no active drug) to determine if there is a noticeable difference in pain relief. The trial seeks individuals who have experienced chronic stomach pain for at least three months and have been diagnosed with non-constipation IBS, such as IBS with diarrhea or mixed symptoms. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potential new therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've had a significant change in antidepressant or pain medications in the last four weeks. Also, you cannot use strong CYP3A4 inhibitors or inducers.

Is there any evidence suggesting that rimegepant is likely to be safe for humans?

Research shows that rimegepant is safe and generally well-tolerated. In earlier studies, individuals used it for migraines without major issues. For instance, taking rimegepant every other day reduced migraine days with only minor side effects, and most people managed the treatment well.

The FDA has already approved rimegepant for treating migraines, indicating its safety for this purpose. When used for migraines, patients usually did not experience severe side effects. This approval provides confidence about its safety for other uses, such as in this trial for irritable bowel syndrome (IBS).

In summary, past research has shown that rimegepant is safe, especially for migraines, and it is expected to be well-tolerated in this new study for IBS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IBS?

Rimegepant is unique because it offers a new approach to treating Irritable Bowel Syndrome (IBS) by utilizing a mechanism originally used for migraine prevention. While most IBS treatments focus on relieving symptoms through dietary changes, fiber supplements, or antispasmodics, rimegepant acts as a calcitonin gene-related peptide (CGRP) receptor antagonist. This mechanism may help alleviate IBS symptoms by reducing inflammation and modulating pain pathways in the gut. Researchers are excited about rimegepant because it offers a novel method of administration through an oral dissolving tablet, potentially offering convenience and rapid symptom relief for IBS sufferers.

What evidence suggests that rimegepant might be an effective treatment for IBS?

Research shows that rimegepant effectively relieves pain, particularly for migraine sufferers. It provides pain relief within two hours for many users. Although rimegepant is approved for treating migraines, this trial will explore its potential to alleviate stomach pain in people with irritable bowel syndrome (IBS). Participants will receive either rimegepant or a placebo to evaluate its benefits for IBS. The researchers aim to determine if rimegepant's pain-relieving properties can also ease IBS-related stomach pain. Early results appear promising, but further research is necessary to confirm its effectiveness for IBS. ^{3 4 6 7 8}

Who Is on the Research Team?

Michael Camilleri, M.D., D.Sc.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-65 with non-constipation IBS and chronic abdominal pain can join this trial. They must have a documented diagnosis, experience significant pain, and be able to consent. Excluded are those with severe depression, substance abuse issues, certain medical conditions like liver or kidney disease, recent changes in pain medication, or women who could be pregnant.

Inclusion Criteria

I am able to understand and agree to the study's procedures and risks.

My pain level is more than 3 on a scale.

I have IBS without constipation and chronic abdominal pain for over 3 months.

Exclusion Criteria

I am not pregnant and will use effective birth control during the trial.

I experience nausea several times a week or daily.

Alcohol or illicit substance dependence or abuse in the past 12 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Participants undergo a 2-week run-in period to establish baseline measurements

2 weeks

Daily diary entries

Treatment

Participants receive either rimegepant or placebo every other day for 4 weeks

4 weeks

Daily diary entries, 1 visit (in-person) for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Rimegepant

Trial Overview The study is testing if Rimegepant (a drug currently used for migraines) can reduce stomach pain in people with Irritable Bowel Syndrome that doesn't involve constipation. Participants will either receive Rimegepant or a placebo to compare the effectiveness.

How Is the Trial Designed?

Group I: rimegepant Experimental Treatment 1 Intervention

* Rimegepant 75mg oral dissolving tablet (ODT) * Formulation and Dosing as FDA-approved for Migraine Prevention: 75 mg Every Other Day (EOD) for 4 weeks/30 days

Group II: placebo Placebo Group 1 Intervention

Placebo ODT appearing identical to the experimental formulation and administered every other day for 4 weeks/30 days

Rimegepant is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in European Union as Vydura for:

• Prophylaxis and acute treatment of migraine in adults

Approved in Canada as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in United Kingdom as Vydura for:

• Prophylaxis and acute treatment of migraine in adults

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Rimegepant significantly improves outcomes for migraine patients, including freedom from pain and pain relief at 2 hours, with odds ratios indicating strong efficacy compared to placebo.

The treatment shows sustained benefits at 24 hours and does not appear to increase the risk of adverse events, suggesting it is a safe option for migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rimegepant for Migraine Patients: A Meta-analysis of Randomized Controlled Studies. Yang, C., Zhang, Y.[2023]

Rimegepant, taken every other day, significantly reduced the mean number of migraine days per month compared to placebo, with a difference of -0.8 days, indicating its efficacy as a preventive treatment for migraines.

The safety profile of rimegepant was comparable to that of placebo, with similar rates of adverse events and no serious safety concerns reported during the study involving 747 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Croop, R., Lipton, RB., Kudrow, D., et al.[2021]

Eluxadoline is a newly approved medication for treating irritable bowel syndrome with diarrhea (IBS-D), showing efficacy in reducing bowel habit changes and abdominal pain in both short and long-term use.

While eluxadoline offers a new treatment option for IBS-D, its use may be limited by a small risk of side effects such as sphincter of Oddi spasm and mild pancreatitis, which need to be considered in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline. Corsetti, M., Whorwell, P.[2018]

Rimegepant is an effective treatment for migraines, showing significant pain relief and reduction in bothersome symptoms compared to placebo in phase III trials, and it can also reduce the number of monthly migraine days when used preventively.

The medication is generally well tolerated, with no signs of liver or heart-related side effects, making it a safe option for adults managing migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: A Review in the Acute Treatment and Preventive Treatment of Migraine. Blair, HA.[2023]

In a study of 418 patients with diarrhea-predominant irritable bowel syndrome (IBS-D), ramosetron, a 5-HT3-receptor antagonist, significantly improved IBS symptoms compared to placebo, with a 47% positive response rate in the treatment group versus 27% in the placebo group.

Ramosetron was well-tolerated with only 7% of patients reporting adverse events, and no serious side effects like severe constipation or ischemic colitis were observed during long-term treatment, indicating its potential safety for extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. Chiba, T., Yamamoto, K., Sato, S., et al.[2021]

Rimegepant (NURTEC ODT®) is an orally disintegrating tablet that acts as a highly-selective antagonist of calcitonin gene-related peptide, specifically designed for the acute treatment of migraines.

In February 2020, rimegepant ODT received its first global approval in the USA for treating migraines with or without aura in adults, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: First Approval. Scott, LJ.[2022]

Ramosetron, a selective 5-HT3 receptor antagonist, has shown significant efficacy in treating irritable bowel syndrome with diarrhea (IBS-D) in two randomized controlled studies involving 957 patients, improving symptom relief compared to placebo.

Ramosetron has a better safety profile than other 5-HT3 receptor antagonists, with a lower incidence of constipation and no reported cases of ischemic colitis, making it a promising treatment option for IBS-D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). Min, YW., Rhee, PL.[2020]

Ramosetron significantly improves overall symptoms of irritable bowel syndrome with diarrhea (IBS-D), including abdominal discomfort and stool consistency, based on a meta-analysis of four trials with 1623 participants.

While ramosetron is effective, it may lead to increased instances of hard stool and constipation, but no serious adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. Qi, Q., Zhang, Y., Chen, F., et al.[2018]

In a rat model of irritable bowel syndrome (IBS), increased levels of 5-hydroxytryptamine (5-HT) and spinal NR2B receptors were linked to visceral hypersensitivity, suggesting their significant role in IBS symptoms.

Treatment with Ro25-6981 (a NR2B antagonist) and amitriptyline (a 5-HT antagonist) reduced the expression of these receptors and inflammatory markers, indicating potential therapeutic effects for managing IBS-related hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. Chen, MX., Chen, Y., Fu, R., et al.[2022]

Rimegepant, an oral CGRP receptor antagonist, has shown significant efficacy in treating migraines, providing pain relief and symptom improvement for up to 48 hours after a single dose, based on completed phase II and III trials.

The medication was well tolerated with only mild to moderate adverse events reported, leading to its FDA approval for acute migraine treatment on February 27, 2020.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant for the treatment of migraine. Negro, A., Martelletti, P.[2021]

Citations

1. ctv.veeva.com ctv.veeva.com/study/comparison-of-rimegepant-and-placebo-for-pain-in-ibs

Comparison of Rimegepant and Placebo for Pain in IBS The primary aim of this study is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS.

2. withpower.com withpower.com/trial/phase-4-irritable-bowel-syndrome-1-2024-cce07

Rimegepant for Irritable Bowel Syndrome Rimegepant significantly improves outcomes for migraine patients, including freedom from pain and pain relief at 2 hours, with odds ratios indicating strong ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11674050/

Real-World Open-Label Experience with Rimegepant for the ... Pain freedom at 2 h was achieved in 45/140 (32.1%) intakes. Regarding the efficacy of the first rimegepant dose (n = 54), significant reductions ...

4. trialx.com trialx.com/clinical-trials/listings/292215/comparison-of-rimegepant-and-placebo-for-pain-in-ibs/

Comparison of Rimegepant and Placebo for Pain in IBS The primary aim of this study is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS.

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06221111/

Trial | NCT06221111 The study hypotheses are: that rimegepant will be safe, well-tolerated, and will improve abdominal pain in participants with non-constipation IBS. The primary ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/88/NCT03266588/Prot_000.pdf

53 ICH E3 1611 Protocol Long term treatment dosing with rimegepant, up to one tablet per day, is safe and well tolerated in the acute treatment of migraine. Page 34 ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/212728Orig1s000MedR.pdf

212728Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov Safety and Efficacy Trial BHV-3000 (Rimegepant) for the Acute ... The primary safety data comes from pooled data from the three pivotal.

8. nurtec.pfizerpro.com nurtec.pfizerpro.com/files/Nurtec_US_Prevention-CHALLENGE_Leave-Behind_Digital_PP-NNT-USA-4370-with-functionality-final.pdf

Sponsored by Eli Lilly, the CHALLENGE-MIG trial did not ... Nurtec ODT Prevention Pivotal Data. Page 2. CHALLENGE-MIG Primary Endpoint and Results1. The proportion of participants with at least a 50% reduction in ...